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01.
arXiv (CS.LG) 2026-06-18

Fair Online Resource Allocation

arXiv:2606.18679v1 Announce Type: cross Abstract: We study the problem of fair online resource allocation, motivated by applications such as refugee resettlement and airline scheduling, where agents arrive sequentially and must be assigned to facilities with limited capacities. We introduce a model that maximizes the overall welfare subject to resource constraints and a Lipschitz fairness requirement, which ensures that similar agents arriving in the same batch receive similar expected outcomes. We first analyze the offline problem, proving that the value of the optimal fair allocation is at least an $\Omega(1/\gamma)$ fraction of the optimal unfair allocation, where $\gamma$ is the fairness coefficient, thereby bounding the price of fairness. For the online setting, we propose an algorithm based on dual mirror descent that enforces fairness constraints within batches while estimating optimal dual variables. We prove that this algorithm achieves sublinear regret relative to the optimal offline fluid benchmark. Finally, we validate our theoretical results using real-world data from the Refugee Economies Programme, demonstrating the algorithm's performance and examining the trade-offs between welfare maximization and fairness enforcement.

02.
arXiv (CS.CL) 2026-06-12

Trait, Not State: The Durability of Reading Identity in Social Highlighting

Prior work on a social web highlighter located individuality in selection – which documents a person chooses to highlight – but measured it cross-sectionally. We ask the temporal question: is a reader's selection signature a trait or a state? We freeze each reader's first six months of highlighting as a profile and track its own-vs-other advantage on their later selections at growing gaps (to 24+ months), with negatives drawn from the same calendar era – so supply drift cannot masquerade as personal drift – at a coarse global level and at a fine level whose negatives and controls come from the reader's own interest neighborhood; the anchor cell reproduces the prior cross-sectional level (+0.188 vs +0.169), validating the harness. Four results. Within the same users, the fine-layer advantage shows no statistically detectable paired decline at any horizon (6-12 month retention R = 1.00 [0.85, 1.18], n = 212; the farthest bin is compatible with a modest decline; the only contrast whose interval excludes zero is the coarse layer at 12-24 months, about 13%). The signal is not reducible to repeated domains (~90% survives excluding all profile sources). Within-person drift is slow (a recent-half profile beats the old half by +0.042). Prospectively, personal profiles – even one built from a reader's earliest documents, median 20 months before evaluation – rank their next reads at roughly 3x the AP of every simple non-personal prior tested. We use "trait" operationally (a stable signature under continued engagement); the scope is heavy, long-tenured readers of one platform, and exposure is not separable from choice.

03.
arXiv (CS.CV) 2026-06-18

ROSA-TFormer: A Radar-Optical Sensor-Aware Temporal Transformer for Pinus sylvestris Plantation Classification in Northern Shaanxi Using GEE-Derived Sentinel-1/2 Time Series

Accurate identification of Pinus sylvestris var. mongolica plantations is important for monitoring afforestation quality and ecological restoration in northern Shaanxi. This paper proposes ROSA-TFormer, a radar-optical sensor-aware temporal Transformer for P. sylvestris classification using Sentinel-1/2 time-series data generated on Google Earth Engine. The model integrates separate SAR and optical embedding branches, a sensor-aware gate, and temporal attention pooling to capture multi-source seasonal features. Experiments on monthly and half-month point-level datasets show that ROSA-TFormer achieves strong classification performance, with 99.67% overall accuracy, 99.56% macro F1, and 98.91% P. sylvestris F1 on the HalfMonth-dataBig dataset. Spatial block validation and ablation results further indicate the effectiveness of radar-optical temporal fusion and sensor-aware modeling. The results demonstrate the potential of ROSA-TFormer for point-level P. sylvestris plantation classification, while broader wall-to-wall validation remains necessary.

04.
arXiv (CS.CV) 2026-06-16

A Survey on 3D Skeleton Based Person Re-Identification: Taxonomy, Advances, Challenges, and Interdisciplinary Prospects

Person re-identification via 3D skeletons is an important emerging research area that attracts increasing attention within the pattern recognition community. With distinctive advantages across various application scenarios, numerous 3D skeleton based person re-identification (SRID) methods with diverse skeleton modeling and learning paradigms have been proposed in recent years. In this paper, we provide a comprehensive review and analysis of recent SRID advances. First of all, we define the SRID task and provide an overview of its origin and major advancements. Secondly, we formulate a systematic taxonomy that organizes existing methods into three categories centered on hand-crafted, sequence-based, and graph-based modeling. Then, we elaborate on the representative models along these three types with an illustration of foundational mechanisms. Meanwhile, we provide an overview of mainstream supervised, self-supervised, and unsupervised SRID learning paradigms and corresponding common methods. A thorough evaluation of state-of-the-art SRID methods is further conducted over various types of benchmarks and protocols to compare their effectiveness, efficiency, and key properties. Finally, we present the key challenges and prospects to advance future research, and highlight interdisciplinary applications of SRID with a case study.

05.
arXiv (CS.CV) 2026-06-16

BRITE: A Benchmark for Reliable and Interpretable T2V Evaluation on Implausible Scenarios

The rapid advancement of photorealistic Text-to-Video (T2V) generation brings in an urgent need for up-to-date evaluation methods. Existing benchmarks largely overlooked implausible scenarios and do not measure audio-visual alignment. We introduce BRITE, the first framework that unifies (1) implausible prompting, (2) fine-grained assessment of audio-visual consistency, and (3) QA-based interpretable evaluation into a comprehensive T2V benchmark. Unlike fully automated Multimodal LLM-based pipelines, which are prone to hallucination and prompt ambiguity, BRITE guarantees reliability through a rigorous human-in-the-loop protocol for benchmark creation. Evaluating five state-of-the-art models (Sora 2, Veo 3.1, Runway Gen4.5, Pixverse V5.5, and Qwen3Max), we reveal a critical performance gap: while models excel at static object composition, they exhibit significant degradation in object-action binding and audio-visual synchronization. Our framework offers the community a reliable, interpretable benchmark and evaluation framework that can detect and locate limitations in the next generation of T2V models, especially for off-manifold prompts

06.
arXiv (CS.CL) 2026-06-12

NOVA: NOise-aware Verbal Confidence CAlibration for Robust Large Language Models in RAG Systems

Accurately assessing model confidence is essential for deploying large language models (LLMs) in mission-critical factual domains. While retrieval-augmented generation (RAG) is widely adopted to improve grounding, confidence calibration in RAG settings remains poorly understood. We conduct a systematic study across four benchmarks, revealing that LLMs exhibit poor calibration performance especially when noisy contexts are retrieved. Specifically, contradictory or irrelevant evidence tends to exacerbate the model's overconfidence issue. To address this, we propose NOVA Rules (NOise-Aware Verbal Confidence CAlibration Rules) to provide a principled foundation for resolving overconfidence under noise. We further design NOVA, a noise-aware calibration framework that synthesizes supervision from ~2K HotpotQA examples guided by these rules. By performing supervised fine-tuning (SFT) with this data, NOVA equips models with intrinsic noise awareness without relying on stronger teacher models. Empirical results show that NOVA yields substantial gains, improving ECE scores by 10.9% in-domain and 8.0% out-of-domain. By bridging the gap between retrieval noise and verbal calibration, NOVA paves the way for both accurate and epistemically reliable LLMs.

07.
bioRxiv (Bioinfo) 2026-06-11

A Deep Hypergraph Learning Model for Predicting Antimicrobial Combination Effects Across Bacterial Targets

Antimicrobial resistance (AMR) creates an urgent need for efficient strategies to identify effective antibacterial combinations. Combination therapy, including antimicrobial peptides (AMPs) paired with conventional antibiotics, is a promising approach, but exhaustive experimental screening across drug pairs and bacterial targets is impractical. This study introduces a hybrid GCN-based hypergraph neural network (HGNN) for predicting antimicrobial-agent combination outcomes against bacterial targets. Each antimicrobial-agent-antimicrobial-agent-bacterium triplet is represented as a ternary hyperedge, enabling the model to learn context-dependent interaction patterns. The framework integrates SMILES-derived molecular graph embeddings for antimicrobial agents, including conventional antibiotics and AMPs, with taxonomy-derived bacterial representations. The prediction task was formulated as a three-class classification problem: synergy, antagonism, and non-interaction. The non-interaction class included experimentally verified indifferent records and synthetic presumed non-interaction triplets generated by negative sampling. Model development used drug-pair-grouped splitting, five-fold grouped cross-validation within the training/validation partition, and final evaluation on a held-out test set. On the held-out three-class test set, the selected GCN-based HGNN achieved an accuracy of 0.83, weighted F1-score of 0.84, macro F1-score of 0.80, and ROC-AUC of 0.95. Per-class evaluation showed accuracies of 0.80 for synergy, 0.92 for antagonism, and 0.85 for non-interaction. Pair-type analysis showed strong performance across AMP-AMP, AMP-conventional antibiotic, and conventional antibiotic-conventional antibiotic combinations. These findings suggest that hypergraph-based representation learning can support computational prioritization of antimicrobial combinations for experimental follow-up. Further studies will be needed to improve model interpretability and to perform prospective validation of predicted synergistic combinations.

08.
medRxiv (Medicine) 2026-06-15

Population-scale genomics reveals divergent pathogenicity of variant classes across paralogous collagen IV genes

Monoallelic pathogenic or likely pathogenic variants in COL4A3 and COL4A4 occur in approximately 1 in 106 individuals, yet whether these paralogous genes confer equivalent pathogenicity for the same variant classes has not been tested at population scale. Using whole-genome sequencing data from the UK Biobank (UKB; n = 500,000), with replication in the All of Us Research Program (n = 414,000), we performed per-variant association testing, gene-based collapsing analyses and phenome-wide association studies (PheWAS) across haematuria, proteinuria and chronic kidney disease. We identified 64 COL4A3 and 92 COL4A4 rare variants significantly associated with haematuria or proteinuria, generating a quantitative allelic series for clinical variant interpretation. Glycine substitutions within collagenous domains conferred similar risks in both genes. In contrast, truncating and non-collagenous domain (NC1) missense variants were strongly associated with haematuria and proteinuria in COL4A4 carriers but showed substantially attenuated or absent associations in COL4A3 carriers despite comparable carrier frequencies and predicted pathogenicity scores. These findings were independently replicated in All of Us. Genome-wide association analysis identified the COL4A3/COL4A4 locus as the dominant genetic determinant of haematuria, with the signal attributable to the aggregate effects of rare coding variants and no evidence of independent common variant or trans-acting modifier effects. These findings demonstrate substantial gene-specific differences in tolerance to truncating and NC1 variants between COL4A3 and COL4A4, challenging assumptions of equivalent pathogenicity across paralogous collagen IV genes. Gene identity and not variant class alone, should inform risk stratification, variant interpretation and genetic counselling in individuals carrying collagen IV risk genotypes.

09.
arXiv (CS.CV) 2026-06-18

LARE: Low-Attention Region Encoding for Text-Image Retrieval

Image retrieval in crowded scenes is particularly challenging due to the salience bias of conventional visual encoders, which tend to focus on dominant objects while neglecting low-attention regions that are often crucial for fine-grained retrieval. We propose LARE (Low-Attention Region Encoding), a framework that explicitly models these overlooked regions. LARE adopts a dual-encoding strategy that encodes low-attention regions of an image and the full image in parallel, leading to more diverse and informative image embeddings. To evaluate image retrieval performance in challenging crowded scenes, we introduce Dense-Set, a challenging subset derived from COCO and Flickr30K. In this subset, images are re-captioned to provide richer descriptions of low-attention or previously overlooked regions. This dataset highlights the limitations of existing retrieval models and enables a more rigorous evaluation under densely crowded scene conditions. Experimental results demonstrate that the proposed framework improves retrieval performance by preserving subtle, non-dominant visual cues within the shared latent space.

10.
arXiv (CS.CV) 2026-06-16

GridVQA-X: A Framework for Evaluating Multimodal Explainability Methods

With the increasing development of Vision-Language Models, it becomes imperative that their predictions are readily explainable to relevant stakeholders. However, the field of explainability has not kept pace with the multimodal surge. While recent Multimodal Explainable AI (MxAI) methods generate explanations to attribute the interaction between different modalities, current evaluation protocols lack the ground truth required to distinguish between true cross-modal reasoning (e.g., spatial composition) and shallow cross-modal shortcuts (e.g., Bag-of-Words attribute matching). It remains unknown whether MxAI methods faithfully capture synergistic interactions or merely hallucinate reasoning on models acting as simple feature detectors. In this paper, we introduce GridVQA-X, the first diagnostic framework specifically designed to evaluate cross-modal explainability. Unlike natural datasets, GridVQA-X leverages a closed-world synthesis logic to generate unique, mathematically guaranteed explanations. We utilize this controlled environment to train paired ground-truth models on identical architectures: $M_{pure}$, which learns robust spatial-relational reasoning and $M_{spur}$, which is structurally forced to rely on cross-modal shortcuts. This behavioral divergence creates a rigorous testbed: a faithful explainer must report distinct reasoning pathways for each model. Our findings reveal that widely used methods fail to distinguish between models relying on genuine spatial-relational reasoning and those exploiting cross-modal shortcuts, highlighting a critical gap in capturing true cross-modal synergy and misrepresenting how multimodal models actually make decisions.

11.
bioRxiv (Bioinfo) 2026-06-18

Looking beyond stereotyped neuron structures reveals links between beading and morphological rearrangements in aging phenotypes.

Understanding how neuronal morphology changes during aging and acute stress is essential for elucidating mechanisms of neurodegeneration. The highly branched PVD neuron of Caenorhabditis elegans provides a powerful model for studying dendritic remodeling and degeneration-associated phenotypes such as dendritic beading. However, the complexity of this arbor presents substantial challenges for automated segmentation and quantitative analysis. In this study, we adapted a convolutional neural network (CNN)-guided region growing framework for automated dendrite tracing, coupled with two topology-based algorithms for categorizing dendritic segments by branching degree. The segmentation algorithm achieved high accuracy relative to manual tracing, with a median Dice coefficient of 0.82, while reducing analysis time by approximately tenfold. Automated dendrite categorization demonstrated strong agreement with manual annotations across branching orders, though position-based mapping performance declined with age due to progressive morphological distortion. Leveraging this platform, we investigated mechanistic differences in dendritic beading patterns observed during aging and cold shock. Consistent with prior work, aging was associated with decreased inter-bead spacing, whereas cold shock produced increased bead dispersion with stress severity. Structural analysis revealed that these trends were not driven by dendritic pruning or reduced arbor complexity. Instead, while a traditional anatomically unflexible paradigm falsely implicated lower-degree dendrites as highly vulnerable, our branching-informed framework revealed that age-dependent beading is fundamentally dictated by a segments history of successive branching events. Conversely, acute cold shock triggered systemic beading that expanded across all dendritic orders in a severity-dependent manner. Together, these findings demonstrate that chronic aging and acute stress engage distinct degenerative pathways (compartment-specific lineage vulnerability versus global architectural collapse) rather than gross morphological loss, as well as highlighting the need for paradigms that enable reliable analysis of changing morphologies.

12.
arXiv (CS.CL) 2026-06-19

NAMESAKES: Probing Identity Memorization in Text-to-Image Models

Text-to-image (T2I) models generate realistic likenesses of some individuals when prompted with their names, raising privacy concerns. However, distinguishing whether a generated face is memorized or fabricated currently requires ground-truth photos, access to training data, or white-box access to model internals, limiting applicability. We introduce a fully black-box behavioral probe that distinguishes between these regimes while requiring no reference photos or prior knowledge of training data. To benchmark this task, we present the NAMESAKES dataset of over one thousand names and faces of public figures spanning a wide range of fame levels, along with perturbed, less famous names. Experiments on state-of-the-art T2I models show that our probe substantially predicts identity memorization and separates memorized from unrecognized names, with further insights into differences across model families.

13.
arXiv (CS.AI) 2026-06-19

Spatial-Aware Reduction Framework: Towards Efficient and Faithful Visual State Space Models

arXiv:2606.19932v1 Announce Type: cross Abstract: Mamba demonstrates strong efficiency in modeling long visual sequences. However, when token reduction is applied to structurally enhanced Mamba variants, these models exhibit a severe performance collapse. We attribute this degradation to the spatially agnostic nature of existing reduction methods, which violate the two-dimensional structural premise required by the selective scanning mechanism. In this work, we propose STORM, a spatial-aware token reduction framework designed to maintain structural integrity throughout the compression process. STORM reformulates reduction into a structured operation on spatial units, enforcing localized constraints to maintain both grid topology and neighborhood coherence. As a plug-and-play module, STORM equips existing reduction pipelines with explicit spatial awareness without any training. Empirical results demonstrate that STORM achieves state-of-the-art pruning accuracy across diverse vision Mamba backbones under training-free settings. Notably, STORM delivers a substantial accuracy recovery on VMamba, outperforming prior methods by up to 63.3\% in top-1 accuracy. Meanwhile, STORM incurs only a 1.0\% accuracy drop on PlainMamba, achieving performance comparable to ViT.

14.
bioRxiv (Bioinfo) 2026-06-20

Ribosomes are covered by a coat of flexible protein fragments

Ribosomal proteins contain flexible terminal regions that are averaged out during electron density reconstructions, rendering them absent from experimental models derived by X-ray crystallography or cryogenic electron microscopy. These flexible protein fragments (FPFs) collectively form an invisible coat on the ribosome surface whose presence has been systematically overlooked. Here we analysed FPFs from 36 ribosomes spanning bacteria, eukaryotes, and mitochondria. We found that mitoribosomes harbour the most numerous and longest FPFs. Structural predictions confirmed that FPFs are predominantly disordered across all ribosome classes. Comparison of FPF amino acid composition against proteome-wide background frequencies revealed strong and domain-specific compositional biases. The balance between arginine and lysine content tracks the cardiolipin content of the membrane each ribosome class contacts. The arginine enrichment in mitoribosomal FPFs may additionally reflect selection arising from the RNA-rich environment of mitochondrial RNA granules, membraneless condensates where mitoribosomes are assembled. FPFs are uniformly depleted in aromatic residues, arguing against protein-driven liquid–liquid phase separation propensity. Our findings suggest that the flexibly tethered coat is a highly functional intrinsic part of all ribosomes.

15.
arXiv (CS.AI) 2026-06-19

Temporal Self-Imitation Learning

arXiv:2606.19752v1 Announce Type: cross Abstract: Long-horizon robot manipulation policies trained with reward shaping can still exploit dense rewards through inefficient interaction, while rare efficient behaviors may be forgotten during training. We argue that temporal efficiency itself provides a powerful and underutilized source of self-supervision for reinforcement learning. We introduce Temporal Self-Imitation Learning (TSIL), a reinforcement learning framework that mines temporally efficient successful trajectories generated during learning and converts them into reusable supervision for future policy improvement. TSIL progressively refines learning using configuration-conditioned adaptive temporal targets derived from fast successful trajectories, while preserving and replaying efficient behaviors through efficiency-weighted self-imitation learning. Across 15 distinct long-horizon manipulation tasks, TSIL consistently improves learning efficiency, task-completion efficiency, revisitation of fast successful behaviors, and robustness to unstable training conditions. More broadly, our results suggest that the temporal structure of successful behavior itself provides a scalable self-supervisory signal for reinforcement learning beyond manually engineered reward shaping alone.

16.
arXiv (CS.CV) 2026-06-16

V2P-Manip: Learning Dexterous Manipulation from Monocular Human Videos

Achieving autonomous robotic dexterous manipulation requires precise, human-like action sequences at scale. As a scalable supplement to costly teleoperation data, extracting trajectories with both visual fidelity and physical plausibility from monocular videos represents a promising frontier in embodied AI. To this end, we introduce V2P-Manip, an efficient framework designed to learn dexterous manipulation policies directly from human demonstration videos. We establish an efficient, integrated pipeline encompassing 3D asset acquisition, trajectory estimation, and dexterous policy learning. To bridge the gap between visual perception and physical constraints, we introduce a two-stage refinement process to enforce spatial alignment and physical consistency. Evaluations on the TACO and OakInk benchmarks demonstrate that our approach significantly outperforms previous methods in pose accuracy, adaptability to unstructured environments, and training efficiency. Ultimately, experimental results confirm an average success rate of over 75% across multiple synthetic manipulation tasks and validate the adaptability of the extracted manipulation priors across diverse dexterous hand embodiments.

17.
arXiv (CS.AI) 2026-06-17

LoopCoder-v2: Only Loop Once for Efficient Test-Time Computation Scaling

arXiv:2606.18023v1 Announce Type: cross Abstract: Looped Transformers scale latent computation by repeatedly applying shared blocks, but sequential looping increases latency and KV-cache memory with the loop count. Parallel loop Transformers (PLT) alleviate this cost through cross-loop position offsets (CLP) and shared-KV gated sliding-window attention, making loop count a practical design choice. We therefore study PLT loop-count selection through a gain–cost view: an extra loop may refine representations, but CLP also introduces a positional mismatch at each loop boundary. We instantiate this study by training LoopCoder-v2, a family of 7B PLT coders with different loop counts, from scratch on 18T tokens, followed by matched instruction tuning and evaluation. Empirically, the two-loop variant delivers broad gains over the non-looped baseline across code generation, code reasoning, agentic software engineering, and tool-use benchmarks, improving SWE-bench Verified from 43.0 to 64.4 points and Multi-SWE from 14.0 to 31.0 points. In contrast, variants with three or more loops regress, revealing a strongly non-monotonic loop-count effect. Our diagnostics show that loop 2 provides the main productive refinement, while later loops yield diminishing, oscillatory updates and reduced representational diversity. Because the CLP-induced mismatch remains roughly fixed as refinement gains shrink, the offset cost increasingly dominates. This gain–cost trade-off explains PLT's saturation at two loops and provides diagnostics for loop-count selection.

18.
arXiv (CS.LG) 2026-06-16

Bridging data-driven priors via the score function for posterior sampling – Comparative review and experimental study

arXiv:2606.14800v1 Announce Type: cross Abstract: This paper reviews how a diverse set of popular data-driven priors commonly used in Bayesian inverse problems can be unified through their respective score functions. By framing these priors under this common perspective, we show that they can benefit from their straightfoward and effective integration into a recently proposed sampling algorithm. The applicability of this common framework is illustrated by considering several data-driven priors, namely regularization-by-denoising, normalizing flow-based priors, score-based generative models, and convex-ridge regularizers. For these four particular priors, the performance of the method is evaluated when conducting image inpainting and single image super-resolution. These results, as well as those obtained when restoring real images acquired in a geological context, demonstrate the efficiency of the method. This unified framework proves versatile enough to handle any posterior distribution defined by a broad class of score function-based priors, beyond the specific cases considered in this paper.

19.
arXiv (CS.LG) 2026-06-16

TreeGRNG: Binary Tree Gaussian Random Number Generator for Efficient Probabilistic AI Hardware

arXiv:2606.16599v1 Announce Type: cross Abstract: Bayesian Neural Networks (BNNs) offer opportunities for greatly enhancing the trustworthiness of conventional neural networks by monitoring the uncertainties in decision-making. A significant drawback for BNN inference at the extreme edge, however, is the imperative need to incorporate Gaussian Random Number Generators (GRNG) within each neuron. State-of-the-art GRNG algorithms heavily depend on multiple arithmetic operations and the use of extensive look-up tables, posing significant implementation challenges for ultra-low power hardware implementations. To overcome this, this paper presents an innovative binary tree random number generator (TreeGRNG) allowing the use of ultra-low-cost constant comparators instead of arithmetic units. We further enhance the TreeGRNG proposal with a set of hardware-aware optimizations exploiting the Gaussian properties. The optimized TreeGRNG surpasses the State-of-the-Art (SoTA) in terms of distribution accuracy while achieving a 3.7$\times$ reduction in energy per sample and boosting the throughput per unit area by 5.8$\times$. Moreover, our TreeGRNG proposal possesses a distinct advantage over the current SoTA in terms of flexibility, as it easily enables designers to adjust the shape of the sampled probability distribution, extending beyond the capabilities of traditional GRNGs, opening the horizon towards future probabilistic AI designs. The TreeGRNG design is available open-source in the link

20.
PLOS Computational Biology 2026-06-22

TCRBinder: Unified pre-trained language model with paired-chain synergy for predicting T-cell receptor binding specificity

作者:

by Weihe Dong, Qiang Yang, Long Xu, Xiaokun Li, Kuanquan Wang, Suyu Dong, Gongning Luo, Xianyu Zhang, Tiansong Yang, Xin Gao, Guohua Wang Deciphering how human T cells recognise peptide-HLA (pHLA) complexes underpins next-generation vaccines and personalised immunotherapies, yet extreme sequence diversity and paired-chains interdependence still hamper reliable in silico prediction of T-cell receptor (TCR) specificity. To overcome these hurdles, we built TCRBinder, a paired-chain-aware deep model with a multi-branch encoder that routes each molecular component through dedicated transformer-based modules to capture contextual signals in both HLA pseudo-sequences and antigenic peptides while simultaneously processing the TCR α and β chains. This design captures the synergistic interaction between paired chains to emulate peptide-HLA-TCR (PHT) interactions and expose residue-level contact motifs. Across PHT and peptide-TCR (pTCR) benchmarks, the model delivered state-of-the-art performance (AUC-ROC = 0.911, AUPR = 0.791 for the PHT task) and remained superior on multiple independent datasets. We tracked the dynamics of clonal expansion and, in a large SARS-CoV-2 repertoire containing completely unseen peptides, improved the AUC-ROC by up to 16.3% over the leading alternatives. Moreover, TCRBinder provided mechanistic insights by pinpointing contact hotspots and quantifying residue contributions to binding probability. These capabilities position TCRBinder as a versatile tool for rational antigen discovery, immunotherapy stratification, and neoantigen vaccine design.

21.
bioRxiv (Bioinfo) 2026-06-11

TifBERT: a self-supervised foundation model for normalization-robust bulk RNA-seq representation learning

Bulk RNA sequencing remains central to translational genomics, yet foundation-model development has largely focused on single-cell data. Existing transformer approaches for bulk RNA-seq often rely on expression discretization, numerical reconstruction, external gene embeddings, or restricted gene sets, limiting robustness across normalization schemes and cohorts. Here, we introduce TifBERT, a self-supervised framework for full-transcriptome bulk RNA-seq representation learning. TifBERT converts each unordered expression profile into a sample-specific gene sequence using term frequency-inverse document frequency (TF-IDF) ordering, prioritizing genes that are both highly expressed within a sample and selectively expressed across the cohort. It is then pretrained using masked gene modeling, predicting gene identities from transcriptomic context rather than reconstructing expression values. Pretrained on harmonized TCGA Pan-Cancer data spanning five RNA-seq normalization schemes, TifBERT learns contextual representations across approximately 10,000 genes without expression binning, landmark-gene restriction, or external biological embeddings. Across 33 TCGA cancer types, TifBERT achieved 90.83% accuracy, 0.996 macro AUC-ROC, and 0.903 MCC. It also captured pathway-level biology, achieving mean sample-wise and pathway-wise Pearson correlations of 0.754 and 0.762 across 1,387 PARADIGM pathway activities. Independent evaluation on GTEx healthy tissues showed preservation of tissue-level transcriptomic structure without retraining. In comparison with existing models, TifBERT achieves competitive subtype discrimination with substantially greater stability and produces markedly richer embedding geometry (effective rank 95.6 versus 6.3), without requiring expression discretization or in-distribution pretraining exposure. Together, TifBERT provides a scalable, normalization-independent foundation model for reusable bulk transcriptomic representation learning

22.
Nature (Science) 2026-06-10

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer

作者:

BRAF gain-of-function mutations, particularly BRAF(V600E), affect roughly 10% of all patients with colorectal cancer (CRC), and portend poor prognosis with limited therapeutic interventions. BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization. Combined inhibition of BRAF and EGFR, although approved therapies, results in short survival benefits and frequent treatment resistance and relapse1–3. Here, through rational chemical library design coupled with parallel proteomic screening, we identified dHuR as a molecular glue degrader of human antigen R (HuR), an RNA-binding protein that drives tumour growth, invasion and therapy resistance. dHuR binds to the CRBN ubiquitin ligase to create a unique benzofuran-tethered composite surface to recruit HuR as a neosubstrate by engaging its β-hairpin G-loop degron, as revealed by the cryo-electron microscopy structure of the ternary complex. dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC. Molecular glue degraders of the RNA-binding protein HuR have therapeutic potential for BRAF-mutant cancers.

23.
arXiv (CS.AI) 2026-06-16

Beyond Correctness: Enhancing Architectural Reasoning in Code LLMs via Scalable Labeling with Agentic Judgment

arXiv:2606.14948v1 Announce Type: cross Abstract: LLMs have substantially improved software engineering yet real-world development requires architectural understanding. Such understanding is prohibitively expensive to label manually and impossible to verify through tests alone. We propose an agentic judging pipeline using a strong LLM as a scalable proxy for expert architectural evaluation, comprising two judges: the Architecture Complexity Judge (ACJ), which estimates codebase-specific architectural understanding a task demands, and the Architecture Quality Judge (AQJ), which evaluates patch conformance to repository-specific architectural conventions via source-grounded rubrics. Fine-tuning Qwen3-8B/14B/32B on 3,360 curated instances achieves resolved rates of up to 27.2% on SWE-bench Verified - up to 540% over the base model and 256% over unfiltered fine-tuning. Meanwhile, the trained models achieve strong cross-language generalization and consistent improvements in architectural patch quality.

24.
arXiv (CS.LG) 2026-06-11

Critic Architecture Matters: Dual vs. Unified Critics for Humanoid Loco-Manipulation

arXiv:2606.11891v1 Announce Type: cross Abstract: Multi-objective reinforcement learning for humanoid robots must coordinate locomotion and manipulation within a single policy. A natural design choice is whether to use a single (unified) critic that estimates the combined value of all objectives, or separate (dual) critics with disjoint reward signals. We present a controlled comparison on the Unitree G1 humanoid (23 active DoF) in NVIDIA Isaac Lab, training loco-manipulation policies through a sequential curriculum spanning 13 levels from stationary reaching to walking with variable-orientation targets. In standardized evaluation, dual-critic policies reach targets 3.5$\times$ faster (6.5 vs. 22.6 simulation steps), achieve 2$\times$ higher throughput (14.3 vs. 7.0 validated reaches per 1,000 steps), and attain higher validated reach rates (65.2% vs. 53.8%) compared to the unified-critic policy. Notably, additional anti-gaming reward mechanisms provide no further improvement beyond the architectural change alone (60.9% vs. 65.2%). These results have direct implications for the emerging paradigm of RL fine-tuning of imitation-learned policies: when refining a pre-trained manipulation policy with RL, a unified critic risks suppressing the learned behavior through competing locomotion gradients. These findings demonstrate that critic architecture is a primary - and often overlooked - design choice in multi-objective humanoid RL, with greater impact than reward engineering on reaching efficiency.

25.
arXiv (CS.CV) 2026-06-11

4DP-QA: Scalable QA for 4D Perception in Vision Language Models

Despite recent advances, Vision Language Models (VLMs) still struggle to grasp the dynamics of the world. We note that the ability to reason about a 4D scene, challenging in itself, is further complicated by two factors. First, VLMs observe motion indirectly via its projection onto 2D images. Second, existing datasets fail to disentangle object and camera motion. To address these challenges, we present a QA generation pipeline that focuses on motion-related scene understanding. We take particular care of the entanglement of camera and object motion by casting tracking in both the traditional way and in a novel, fixed reference system, dubbed True-Motion Tracking, which provides an intuitive description of motion. From this pipeline, we generate a large-scale training dataset of 400K samples, 4DP-QA (4D Perception QA), and a 2.2K-sample benchmark, 4DP-QA-Bench. Training existing models on our dataset yields performance improvements on an external benchmark, validating the effectiveness of our method.